Résumé
It was recently shown that cholecystokinin (CCK)-related peptides, CCK-8S, CCK-8NS and Ceruletide, could induce neuroprotection against the glutamate neurotoxicity, either in vitro on rat neuronal cultures, or in vivo on global ischemia models in gerbils. We previously developed an hypoxia model using carbon monoxide (CO)-intoxicated mice and reported that the CO-induced amnesia is closely related to glutamate neurotoxicity. We therefore investigated the effect of systemic Ceruletide on CO-induced amnesia. Male ddY mice, weighing 30-35 g, were exposed three consecutive times to CO (10 ml/min, 30-50 sec, 1 hr between each exposure). Impairment of working memory was examined five days after, using spontaneous alternation behavior in the Y-maze. Amnesia was also examined seven days after CO exposure using a passive avoidance test. In both tests, Ceruletide (administered s.c. once 30 min before the first CO exposure) significantly reversed CO-induced impairment of memory at doses of 30 and 100 μg/kg. The extent of protection is dependent upon the mode of administration of Ceruletide (30 min before or immediatly after CO) and the severity of hypoxia (increased by maintaining body temperature of the mice at 38℃ using a hot plate). These results confirmed previous observations that the CO-induced hypoxia could be used as an alternate for ischemia models and that CCK-related peptides are neuroprotective agents against glutamate neurotoxicity. The exact implication of CCK neurotransmission in the neurotoxicity is currently under investigation using the same paradigm.